The Journal of Experimental Medicine
Torrey Pines Biolabs
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Published online 28 December 2004 doi:10.1084/jem.20041277
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 1, 83-93
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ARTICLE

 Identification and characterization of an endogenous chemotactic ligand specific for FPRL2

Isabelle Migeotte1, Elena Riboldi3, Jean-Denis Franssen4, Françoise Grégoire2, Cécile Loison4, Valérie Wittamer1, Michel Detheux4, Patrick Robberecht2, Sabine Costagliola1, Gilbert Vassart1, Silvano Sozzani3,5, Marc Parmentier1, and David Communi1

1 Institut de Recherche en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
2 Laboratoire de Chimie Biologique et de la Nutrition, Université Libre de Bruxelles Campus Erasme, B-1070 Brussels, Belgium
3 Section of General Pathology and Immunology, University of Brescia, 25121 Brescia, Italy
4 Euroscreen s.a., B-6041 Gosselies, Belgium
5 Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy

CORRESPONDENCE Marc Parmentier: mparment{at}ulb.ac.be

Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein–coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal–regulated kinase 1/2 mitogen-activated protein kinases through the Gi class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2.

Abbreviations used: ERK, extracellular signal–regulated kinase; FPR, formyl peptide receptor; FPRL, FPR-like receptor; GPCR, G protein–coupled receptor; HBP, heme-binding protein; MAP, mitogen-activated protein; SEC, size-exclusion column.


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